The object of this invention is a tip with a mantle wall defining a sample space, for receiving a liquid sample, the tip having a first open end to be inserted into a liquid and a second open end for attaching the tip to a suction device, such as a mechanical or electronic pipette, intended for dispensing, transferring, diluting, titrating, mixing, or a combination of all, or some of these operations.
The object of the invention is also a method for dispensing, transferring, diluting, titrating, mixing, or a combination of all, or some of these operations with a suction device, such as a mechanical or electronic pipette having an end part, which encloses a cylindrical space having a reciprocating means, such as a plunger, and having a removably attached tip.
The said suction devices comprise a body and an associated end part, the open end of which being directed away from the body for removably attaching a disposable tip having a sample space for receiving a liquid sample, the end part encloses the cylindrical space having a reciprocatingly movable means, a plunger, for receiving a sample and for removing it therefrom.
When in the following description the words xe2x80x98suction devicexe2x80x99 or xe2x80x98pipettexe2x80x99 are used, they generally mean all types of suction devices defined above, which suction devices function as pipettes, dispensers, diluter, titraters, or mixers, or in addition as a combination of all or some of these operations. A mechanical or an electronic pipette can be a manually operated separate device or part of some apparatus, of an analysing device, etc.
Over approximately the past three decades pipettes have been in use having attached liquid reservoirs, that is pipette tips, from which liquid has escaped to the inner parts of the pipette, for example due to careless operation of the pipette, or in the form of liquid molecules vaporized from the liquid. The contamination of the inner parts of the pipette has jeopardized labour safety and reduced or even completely terminated the reliable operation of the pipette itself. Naturally this cannot be accepted in laboratory work, which has to be precise as well as safe to users and patients. Also in scientific or in other such work this is not allowed.
Due to these problems pipette manufacturers recommend that the pipettes are disassembled and cleaned at regular intervals by the pipette users. In this procedure almost always also the plunger and the gasket of the pipette are re-lubricated and often also the pipette has to be re-calibrated, i.e. the pipetted, dispensed etc. liquid volumes are set to correspond to the volumes set on the scale of the pipette. This disassembling and reassembling of the pipette, in addition to being an inconvenient and laborious procedure, does not guarantee that the pipette would not contain infection agents or other contamination such as DNA- and RNase-contamination which interferes with PCR-work. Therefore some pipette manufacturers have started to manufacture pipettes, which are claimed to be sterilizable in an autoclave. Sterilization in the autoclave does not, however, remove DNA- and RNase-contamination from the pipette parts. It is a very tedious operation and often the operation itself damages parts of the pipette to such an extent that the pipette will not function sufficiently accurately and reliably any more. When the pipette is used after the sterilization, it is possible that it will be contaminated already with the first pipetting.
U.S. Pat. No. 5,406,856 discloses a suction device which is meant to be used with such disposable tips, which have a tip portion to be inserted into a liquid, the tip portion having an opening for taking a liquid sample and removing it and in which disposable tips the part to be adapted onto the end of the body of the suction device is closed towards the suction device. The form of this closed part and simultaneously its volume can be changed with a means within the end part of the body of the suction device. In this solution the contamination can be prevented, but the disposable tip used is a special tip.
U.S. Pat. No. 4,444,062 discloses a multichannel suction device having a flexible membrane mounted between the body of the suction device and an attached tipstand so, that the rods in the plunger movable within the body of the suction device come into contact with the membrane, when the plunger is pushed downwards. In this solution the membrane is secured either on the undersurface of the body or on the upper surface of the tipstand or two membranes are used of which the first one is secured on the undersurface of the body and the second one on the upper surface of the tipstand. The tipstand itself is mounted to the body with a screw connection. In an embodiment of this invention, the tipstand assembly consisting of a tipstand with attached tubes and tips attached to these and a membrane secured onto the upper surface of the tipstand can be one disposable moulded plastic unit which is mounted to the body of the suction device with a suitable quick connection method. In this publication, nothing is disclosed of the removal of the tipstand, tipstand assembly, or its parts from the body with a movement of the plunger or some other means, such as a tip remover or other such means.
The disadvantages cited above can be avoided by using the solution for the disposable tip according to the invention. It is characterizing for the tip according to the invention that the tip is provided with a membrane means closing the gas and liquid passage in a gas and liquid tight manner from the first end of the tip to the suction device, when the tip is attached to the suction device, the membrane means comprising a membrane made of a gas and liquid impermeable, flexible, reversibly deformable material. The solution according to the invention prevents liquids to be dispensed and/or gases vaporizing therefrom from entering the inner parts of the pipette. In addition, the tip according to the Invention can be removed with the movement of the plunger or other similarly functioning means, which increases the ergonomy of the use of the pipette and working safety.
The object of the invention is also a method, which is characterized in that the reciprocatingly movable means within the cylindrical space enclosed by the end part of the suction device, is brought into contact with a membrane means in the sample space of the tip, the membrane means comprising a membrane, which is made of a gas and liquid impermeable, flexible, reversibly deformable material, for changing the volume delimited by the membrane from the sample space of the tip for taking a sample and/or removing it, and that the tip is removed from the end part of the suction device by translating the movement of the means to the tip.
The suction device itself used with the disposable tip, can be as such a known manually operated or e.g. electrical, and it can be independently operated or functioning as a part of some apparatus, e.g. pipette.
The disposable tip according to a preferred embodiment of the invention is attached to the end part of the suction device preferably against the inner wall of the cylindrical space within the end part with a friction joint. In another preferred embodiment according to the invention the disposable tip is attached e.g. with a friction joint against an inner, conical surface widening towards the end of the end part. The said cylindrical space or the said conical surface can also be provided with shoulders or projections, against which the disposable tip comes into contact when attached.
The disposable tip according to another preferred embodiment of the invention can also be attached onto the end of the end part of the suction device by using a suitable mounting means, such as a sleeve, attachable e.g. with a friction joint, and to which the disposable tip is attached e.g. with suitable holding means, such as projections.
Still in another preferred embodiment of the invention, the tip according to the invention can also be attached on the distal end of the end part of the suction device preferably with a friction joint.
According to the invention the tip is provided with a membrane means mounted into the sample space of the tip, the membrane means comprising a membrane made of a material, which is impermeable to air and liquids, is flexible, and reversibly deformable, in order to close the gas and liquid passage in a gas- and liquid-light manner from the first open end of the tip to the suction device, when the tip is attached to the suction device, whereby the means in the cylindrical space, moving reciprocatingly in the cylindrical space within the end part of the body of the suction device, when extending through an opening in the end part of the body into the sample space of the disposable tip, can be brought in contact with the said membrane to bring about a change in the volume delimited by the membrane means from the sample space of the disposable tip, for taking a sample and removing it.
According to a preferred embodiment of the invention, the mantle wall defining the sample space is rigid. In another preferred embodiment of the invention, the membrane of the membrane means is essentially stretched.
According to the invention the end of the sample space of the disposable tip facing the suction device is closed in a gas- and liquid-tight manner with a membrane, which is made of a flexible, reversibly deformable material, impermeable to air and liquids, whereby the means, such as a plunger, reciprocatingly moving in the cylindrical space within the end part of the body of the suction device, can be brought in contact with the said membrane for bringing about a change in the volume of the sample space of the disposable tip for taking a sample and/or removing it.
The form of the membrane depends naturally on the form of the sample space. According to a preferred embodiment of the invention, the membrane is secured to that surface of the mantle, which is facing the suction device e.g. by welding or gluing in connection with the manufacture of the disposable tip. The membrane can also be secured with corresponding methods onto the outer surface of the mantle defining the sample space of the tip in the vicinity of the second open end of the tip. In a preferred embodiment of the invention, the membrane is secured to the second end of the disposable tip device with a circular sleeve, to seal the membrane against the surface of the mantle defining the sample space of the disposable tip. In another preferred embodiment of the invention, the said circular sleeve comes into contact with a shoulder or a projection on the outer surface of the said mantle wall, thereby sealing the membrane against the surface of the said mantle wall.
In another preferred embodiment, the membrane is mounted to a frame, which in turn can be mounted in a gas- and liquid-tight manner into the said second open end of the tip and where it stays in the intended position e.g. under the influence of a friction force, preferably without any special mounting means.
In a preferred embodiment of the invention the said frame can be of a detachable kind.
According a preferred embodiment of the invention, the membrane means is sealingly adapted in the sample space in connection with the manufacturing of the disposable tip e.g. by welding or gluing. According to another preferred embodiment the membrane is secured to a frame, which can be adapted in a gas- and liquid-tight manner against the inside surface of the sample space of the disposable tip, and where it stays in its intended position e.g. under the influence of a friction force, preferably without any special mounting means. The membrane means can also be attached onto the inside surface of the sample space of the disposable tip by means of shoulders, projections, pegs, or other similar means on the inside surface of the disposable tip.
According to the invention the disposable tip can be detached from the end part of the suction device by causing the movement of the plunger moving in the cylindrical air space to be translated into a removal movement of the tip.
According to a preferred embodiment of the invention, the end of the disposable tip facing the suction device can thus be brought in contact with the plunger or with shoulders, pegs, or other similar means associated with the plunger for removing the disposable tip from the end part of the suction device with a movement of the plunger. Preferably the mantle defining the sample space of the disposable tip forms a surface in the second end of the disposable tip, against which surface the plunger moving within the cylindrical space or a shoulder at the end of the plunger can be brought in contact for removing the disposable tip with the movement of the plunger. Also a frame, onto which the membrane is secured, or a said circular sleeve used for securing the membrane, can form a surface against which the plunger or means associated therewith can be brought in contact for removing the disposable tip with the movement of the plunger.
In a preferred embodiment of the invention the membrane is secured to a frame having means, which can be brought in contact with the plunger, moving within the cylindrical air space of the end part of the suction device, or with shoulders, pegs, or other similar means belonging to the plunger, for removing the disposable tip and the membrane means with its frame mounted therein from the end part of the suction device with the movement of the plunger out of the opening of the end part of the suction device.
The tip according to the invention can be adapted also to laboratory work based on the PCR-technique, because the membrane means according to the invention in the disposable tip prevents the inner parts of the pipette from DNA- and RNase-contamination and thus the cross-contamination of different samples and reaction mixtures.
Further scope of the applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.